Cafaro Alessandro, Foca Flavia, Nanni Oriana, Chiumente Marco, Coppola Marina, Baldo Paolo, Orzetti Sabrina, Enrico Fiorenza, Ladisa Vito, Lerose Rosa, Nardulli Patrizia, Maiolino Piera, Gradellini Federica, Gasbarro Anna Rita, Carrucciu Gisella, Provasi Riccardo, Cappelletto Paola Cristina, Pasqualini Alessandra, Vecchia Stefano, Veraldi Marianna, De Francesco Adele Emanuela, Crinò Lucio, Delmonte Angelo, Masini Carla
Pharmacy Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Front Oncol. 2024 Mar 27;14:1351995. doi: 10.3389/fonc.2024.1351995. eCollection 2024.
The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known and driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program.
PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability.
Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate.
The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily.
III期KEYNOTE-189试验确立了帕博利珠单抗联合培美曲塞和铂类作为无已知驱动基因突变且不依赖程序性细胞死亡配体1（PD-L1）表达的IV期非小细胞肺癌（NSCLC）患者的一线标准治疗方案。然而，在意大利，国家医疗服务支付计划的资格仅限于PD-L1＜50%的患者。PEMBROREAL研究评估了帕博利珠单抗在符合国家医疗服务支付计划资格的患者中的真实疗效和安全性。
PEMBROREAL是一项针对在2019年12月至2020年12月可报销时间窗内开始接受帕博利珠单抗联合培美曲塞和铂类治疗的NSCLC患者的回顾性观察性研究。主要终点是评估无进展生存期（PFS）和总生存期（OS；采用Kaplan-Meier方法）、治疗反应和耐受性。
截至2022年2月，已观察到279例患者（中位随访时间：19.7个月）。中位PFS为8.0个月（95%置信区间：6.5-9.2）。OS未达到，但我们可以估计联合治疗的12至24个月生存率分别为66.1%和52.5%。PD-L1表达和东部肿瘤协作组（ECOG）体能状态均与PFS和OS相关。总体而言，只有44.4%的患者报告了不良事件，而毒性导致的停药率为5.4%。
PEMBROREAL研究结果表明，尽管与KEYNOTE-189研究相比患者人口统计学和病理特征存在差异，但帕博利珠单抗联合培美曲塞和铂类的联合治疗对转移性非鳞状NSCLC有效，即使对于PD-L1水平低于50%的患者也是如此。研究期间报告的不良事件更具化疗治疗而非免疫治疗的典型特征，医生能够轻松处理。
